The present invention relates to an apparatus for measuring a blood volume which is ejected with each heartbeat, and also to a method of evaluating a result of measurement by such apparatus.
In medical facilities, variation in the hemodynamics of a patient in an operating room, an intensive care unit, an emergency room, a dialysis treatment room, or the like needs to be monitored continuously as long as possible. Conventionally, monitoring of the variation in the hemodynamics of such a patient has been predominantly carried out by direct monitoring of a blood pressure. In a living body, a cardiac output and a vascular resistance are regulated such that the blood pressure of the centrum is limited within a predetermined range. In order to know the variation in the hemodynamics of the patient in an early stage, therefore, it is not enough to only monitor the blood pressure directly, and there is a need to know cause of change in the blood pressure when the change in blood pressure is observed. For this reason, there is a need to monitor a change of the cardiac output, in addition to monitoring the change in the blood pressure.
A method and apparatus for measuring a blood volume, and a biological signal monitoring apparatus are known in which variation in hemodynamics of the patient can be monitored always and continuously in an noninvasive manner, a skilled technique of a medical person such as insertion of a catheter is not required, less pain is experienced by the patient, there is no threat of infection because it is noninvasive, and the cost is low (see JP-A-2005-312947).
JP-A-2005-312947 discloses the principle of measuring the blood volume (cardiac output) which is ejected with each heartbeat in the following manner.
When a Windkessel model shown in FIG. 4 is used, the influx flow volume to the aorta during a systole, that is, the flow volume (SV−Qs) acquired by deducting the efflux flow volume to the periphery during a systole Qs from one stroke volume SV is represented by the aortic compliance C and the pulse pressure PP (see Expression 1). In this description, the narrowly defined pulse pressure (the difference between the systolic blood pressure and the diastolic blood pressure) is indicated by PP, and the broadly defined pulse pressure (the systolic blood pressure (maximum value), the diastolic blood pressure (minimum value), or the difference between them, the mean blood pressure, and the like) is indicated by BP.SV−Qs=C·PP  (Exp. 1)
The efflux flow volume to the periphery during a diastole Qd is equal to (SV−Qs).
Furthermore, Qs and Qd represent values acquired by dividing the systolic and diastolic arterial pressures V by the vascular resistance R and then multiplying by the systolic duration Ts and the diastolic duration Td, respectively. However, as it is estimated, for the matter of simplicity, that the flow volume values are proportional to Ts and Td, respectively, the values may be represented by Expression 2.(Qd=)SV−Qs=SV·Td/(Ts+Td)  (Exp. 2)
From Expressions 1 and 2, Expression 3 is acquired as follows.SV·Td/(Ts+Td)=C·PPSV=C·PP·(1+Ts/Td)  (Exp. 3)
Here, when it is assumed that C and Ts/Td remain constant during the measurement period, and C·(1+Ts/Td) is represented by K, the following is acquired.SV=K·PP  (Exp. 4)PP=SV/K  (Exp. 5)
In this way, according to the Windkessel model, the pulse pressure is proportional to SV.
In practice, actually measured pulse pressure PP1 is configured by the pulse pressure PP2 (although this is represented by PP in Expression 5, hereinafter it will be represented by PP2), and the augmentation PP3 in the pulse pressure observed upon administration of a vasoconstrictor or the like, as in following Expression 6.PP1=PP2+PP3  (Exp. 6)
In a case where PP3 is not observed, Expressions 4 and 6 lead to:SV=K·PP1  (Exp. 7)
Therefore, SV can be directly measured from the measurement of blood pressure. However, since PP1 already includes PP3 in the administration of a vasoconstrictor or the like, SV would be overestimated.
This has been a problem when SV is calculated from the blood pressure.
With regard to the accuracy in measurement of an apparatus which enables calculation of the stroke volume as well as the cardiac output from the waveform of the arterial pressure measured invasively, the following is reported: “For a patient admitted to the ICU (intensive care unit) after a surgery, when the vascular resistance changed by about 60% upon administration of a vasoconstrictor phenylephrine, a remarkably large bias was observed between the measurements by the apparatus described above and the measurements by the cardiac output computer operating in the thermodilution mode used as the standard method, the values of the former being greater than those of the latter. In that case, there is accordingly a need for re-calibration by the blood volume flowmeter operating in the thermodilution mode.” Further, in the administration of a vasoconstrictor, it is known that, in the administration of a vasoconstrictor or the like, the pulse pressure increases by influence of a reflected wave from the periphery, and PP3 corresponds to this augmentation.
In electrocardiography, the pulse wave propagation time (hereinafter, referred to as PWTT), which corresponds to a time taken until the reach of the propagated pulse wave to the SpO2 at the periphery, is configured by following Expression 8.PWTT=PEP+PWTT1+PWTT2  (Exp. 8)
Here, as shown in FIG. 9, PEP is the pre-ejection period of the heart, which is the duration from the initiation of electric stimulation of the heart to the opening of the aortic valve. PWTT1 is a time taken for the pulse wave to be propagated from its generation in the aorta after the opening of the aortic valve to an artery at the periphery where typically blood pressure measurement is conducted invasively. PWTT2 is a time taken for the pulse wave to be further propagated from the artery at the periphery to a peripheral blood vessel where photoplethysmogram is measured.
The duration of (PEP+PWTT1) from the R wave of electrocardiogram (ECG) to the onset of rising in the pulse wave at the femoral artery was measured using ten adult dogs, and measured the relationship between the duration of (PEP+PWTT1) and the pulse pressure with administration of a vasoconstrictor in the respective cases under conditions such as, administration of a vasodilator, increase of the myocardial contractility, attenuation of myocardiac contractility, and blood removal. In this way, it was found good correlation between the pulse pressure PP1 and the duration of (PEP+PWTT1).
FIG. 5 is a view showing the representative relationship between the PWTT and the pulse pressure PP.
Therefore, the relationship between the pulse pressure PP1 and (PEP+PWTT1) can be represented by following Expression 9.PEP+PWTT1=a·PP1+b  (Exp. 9)
Further, the relationship between PWTT2 and PP1 is represented by following Expression 10.PWTT2=c·PP1+d+e  (Exp. 10)
Since it was discovered that, in a case where PP3 appears with the use of a vasoconstrictor, PWTT2 tends to be prolonged as compared to cases under other conditions, a portion corresponding to this prolongation is represented by “e” (where, e is not limited to a constant).
Substituting Expressions 9 and 10 for Expression 8, Equation 11 is acquired as follows.PWTT=(a·PP1+b)+(c·PP1+d+e)PP1=(PWTT−b−d−e)/(a+c)  (Exp. 11)
As PP2 in Expression 6 is replaced with the right-hand side of Expression 5, following Expression 12 is acquired.PP1=SV/K+PP3  (Exp. 12)
From Expressions 11 and 12, the following Expression 13 is acquired.PWTT/(a+c)−(b+d)/(a+c)=SV/K+PP3+e/(a+c)SV=K·(PWTT/(a+c)−(b+d)/(a+c))−K·(PP3+e/(a+c))  (Exp. 13)
As described above, it has been experimentally found that PWTT2 tends to be prolonged when PP3 is observed upon use of a vasoconstrictor or the like. FIG. 8 shows this relationship.
When phenylephrine is administered, PP3 is observed and accordingly PP1 is increased, as shown in FIG. 8. However, the relationship between PWTT2 and PP1 which may be observed in cases of blood removal or administration of pentobarbital is no longer observed with the administration of phenylephrine, and PWTT2 shows a tendency to be prolonged.
Therefore, it has been experimentally discovered that, as shown in FIG. 7, there is maintained a negative correlation between SV and PWTT even upon administration of phenylephrine, which may be still observed under different conditions, and thus the second term (K·(PP3+e/(a+c))) in the right-hand side of Expression 13 may be substantially ignored.
Here, taking 1/(a+c)=α and −(b+d)/(a+c)=β, following Expression 14 is acquired.SV=K·(α·PWTT+β)  (Exp. 14)
where α and β are empirically acquired coefficients that are inherent to the patient.
Moreover, the cardiac output can be calculated from following Expression 15.esCO=K·(α·PWTT+β)·HR  (Exp. 15)wherein esCO [L/min] is the cardiac output, and K is an empirically acquired constant which is inherent to the patient. HR is a heart rate of the patient.
In addition, Expression 15 may be substituted in the same way as in Expression 16.esCO=(αK·PWTT+βK)·HR  (Exp. 16)
where αK and βK are empirically acquired coefficients which are inherent to the patient.
When SV and esCO are calculated using PWTT as expressed in Expressions 14, 15 and 16, as shown in FIG. 7, there is maintained correlation between SV and PWTT which may be observed under different conditions, even in a case of an augmentation in the pulse pressure associated with the use of a vasoconstrictor, as shown in FIG. 6, and thus problems that can be seen with the conventional practice of calculating SV by blood pressure may be solved.
Naturally, there is no risk of overestimation of CO.
FIGS. 6 and 7 show relationships between SV and PP1 and between SV and PWTT as measured during vascular constriction, blood removal, and cardiac suppression in an animal test.
Incidentally, there occurred an increase in the vascular resistance by more than 60% upon administration of phenylephrine.
Next, an example of a biological signal monitoring apparatus to which the conventional method of measuring a blood volume is applied will be described in detail with reference to the drawings.
FIG. 10 is a block diagram illustrating the configuration of the example of the conventional biological signal monitoring apparatus, and FIG. 11 is a diagram illustrating an example of the manner of a measurement in which the conventional biological signal monitoring apparatus. FIG. 9 is a view showing waveforms of measured pulse waves.
A systolic/diastolic blood pressure measuring unit 20 includes a cuff 25, a compressing pump 27, a pressure sensor 28, a cuff pressure detector 29, an A/D converter 22, and the like, as shown in FIG. 10.
Specifically, the cuff 25 is attached to an upper arm of a patient for measurement, as shown in FIG. 11. In the cuff 25, the interior is opened or closed with respect to the atmosphere by an exhaust valve 26 installed in a body 10 of the biological signal monitoring apparatus. Air is supplied to the cuff 25 by the compressing pump 27 installed in the body 10 of the biological signal monitoring apparatus. The pressure sensor 28 (cuff pulse wave sensor) is mounted in the body 10 of the biological signal monitoring apparatus, and an output of the sensor is detected by the cuff pressure detector 29.
An output of the cuff pressure detector 29 is converted into a digital signal by the A/D converter 22, and input to a cardiac output calculating unit 40 (in FIG. 11, the cuff pressure detector 29, the A/D converter 22, and the cardiac output calculating unit 40 are included in the body 10 of the biological signal monitoring apparatus).
In FIG. 9, (a) shows an electrocardiogram waveform, and an aortic pressure wave immediately after the ejection from the heart has a waveform shown in (b) of FIG. 9. Further, waveforms of an arterial pressure wave at the periphery and a peripheral pulse wave are acquired as shown (c) and (d) of FIG. 9.
As shown in FIG. 10, a pulse wave propagation time measuring unit 30 includes a time interval detection reference point measuring unit 31, an A/D converter 32, a photoplethysmogram sensor 33, a pulse wave detector 34, an A/D converter 35, etc.
The time interval detection reference point measuring unit 31 is used for detecting a point of time when an R wave is generated on an electrocardiogram, and an output thereof is converted into a digital signal by the A/D converter 32, and then input to the cardiac output calculating unit 40. Specifically, the time interval detection reference point measuring unit 31 is configured by ECG electrodes 31a (electrocardiogram measuring unit) which are attached to the chest of the subject, as illustrated in FIG. 11. Measurement data is transmitted from a measurement data transmitter 50 which is electrically connected to the ECG electrodes 31a, to the body 10 of the biological signal monitoring apparatus in a wireless manner. The transmitted measurement data is converted into a digital signal by the A/D converter 32 in the body 10 of the biological signal monitoring apparatus, and then input to the cardiac output calculating unit 40. In this way, the ECG waveform as shown in (a) of FIG. 9 is acquired.
Meanwhile, the photoplethysmogram sensor 33 is intended to be attached to a peripheral part, such as a finger, of the patient, as shown in FIG. 11, and to be used in acquiring the pulse wave propagation time, for example, by performing SpO2 measurement. The photoplethysmogram sensor 33 is electrically connected to the measurement data transmitter 50, and the measurement data transmitter 50 transmits the measurement data to the main body 10 of the biological signal monitoring apparatus in a wireless manner. When the measurement data is sent to the pulse wave detector 34 in the main body 10 of the biological signal monitoring apparatus, the pulse wave (photoplethysmogram) at the attachment location of the patient is detected. The output of the pulse wave detector 34 is converted into a digital signal by the A/D converter 35 and then input to the cardiac output calculating unit 40. As such, a waveform of the photoplethysmogram (a waveform at the periphery) such as shown in (d) of FIG. 9 is acquired.
Next, a calculation process of acquiring esCO from the Expressions 15 and 16 will be described with reference to FIGS. 12 to 15.
First, the procedure in which βK is acquired by calibration using a default value of αK and then esCO is calculated will be described with reference to FIG. 12.
Reading of the default value of αK is carried out (Step S1). PWTT and HR are acquired (Step S2). Next, it is determined whether βK is available or not (Step S3). If the determination in Step S3 is NO, then a request for input of cardiac output (CO) value for calibration is displayed (Step S4). It is determined whether the CO value for calibration has been input or not (Step S5). If the determination in Step S5 is YES, the input CO value, and the acquired PWTT and HR are stored in a register as CO1, PWTT1, and HR1, respectively (Step S6). βK is acquired from following Expression 17 (Step S7).βK=CO1/HR1−αK·PWTT1.  (Exp. 17)
Calculation of acquiring esCO from the Expression 16 is carried out by using the acquired βK (Step S8). If the determination in Step S3 is YES, likewise, calculation of acquiring esCO from the Expression 16 is carried out (Step S8). The esCO acquired in the calculation is displayed (Step S9).
The above procedure is repeated as required.
Next, the procedure in which αK and βK are acquired by calibration and then esCO is calculated will be described with reference to FIG. 13. Reading of the default value of αK is carried out (Step S1). PWTT and HR are acquired (Step S2). Next, it is determined whether βK is available or not (Step S3).
If the determination in Step S3 is NO, then a request for input of CO value for calibration is displayed (Step S4). It is determined whether the CO value for calibration has been input or not (Step S5). If the determination in Step S5 is YES, the input CO value, and the acquired PWTT and HR are stored in a register as C01, PWTT1, and HR1, respectively (Step S6). βK is acquired from the Expression 17 (Step S7). Calculation of acquiring esCO from the Expression 16 is carried out by using the acquired βK (Step S8). If the determination in Step S3 is YES, it is determined whether re-calibration for αK should be carried out or not (Step S10). If the determination in Step S10 is NO, likewise, calculation of acquiring esCO from the Expression 16 is carried out (Step S8). If the determination in Step S10 is YES, a request for input of the CO value for calibration is displayed (Step S11). It is determined whether the CO value for calibration has been input or not (Step S12). If the determination in Step S12 is YES, the input CO value, and the acquired PWTT and HR are stored in the register as CO2, PWTT2, and HR2, respectively (Step S13). αK and βK are calculated from following Expressions 18 and 19 (Step S14).CO1=(αK·PWTT1+βK)·HR1  (Exp. 18)CO2=(αK·PWTT2+βK)·HR2  (Exp. 19)
Calculation of acquiring esCO from the Expression 16 is carried out by using the acquired αK and βK (Step S8). If the determination in Step S10 is NO, calculation of acquiring esCO from the Expression 16 is carried out (Step S8). The esCO acquired in the calculation is displayed (Step S9).
The above procedure is repeated as required.
Then, the procedure in which a is the default value, β and K are acquired by calibration, and then esCO is calculated will be described with reference to FIG. 14. The calibration of β is carried out when the pulse pressure is not augmented by administration of a vasoconstrictor or the like.
Reading of the default value of a is carried out (Step S1). PWTT and HR are acquired (Step S2). Next, it is determined whether β is available or not (Step S15). If the determination in Step S15 is NO, then a request for measurement of blood pressure for calibration is displayed (Step S16). It is determined whether measurement of the blood pressure for calibration has been conducted or not (Step S17). If the determination in Step S17 is YES, the measured PP value, and the acquired PWTT and HR are stored in the register as PP1, PWTT1, and HR1, respectively (Step S18). β is calculated from following Expression 20 (Step s19).β=PP1−α·PWTT1  (Exp. 20)
If the determination in Step S15 is YES, or after β is calculated in Step S19, it is determined whether K is available or not (Step S20). If the determination in Step S20 is NO, a request for input of CO value for calibration is displayed (Step S21). It is determined whether the CO value for calibration has been input or not (Step S22). If the determination in Step S22 is YES, the input CO value is stored in the register as CO1 (Step S23). K is calculated from following Expression 21 (Step S24).K=CO1/{(α·PWTT1+β)·HR1}  (Exp. 21)
If the determination in Step S20 is YES, or after K is calculated in Step S24, esCO is calculated from the Expression (Step S25). The esCO acquired in the calculation is displayed (Step S26).
The above procedure is repeated as required.
Then, the procedure in which α, β, and K are acquired by calibration, and then esCO is calculated will be described with reference to FIG. 15. The calibration of α and β is carried out when the pulse pressure is not augmented by administration of a vasoconstrictor or the like.
Reading of the default value of α is carried out (Step S1). PWTT and HR are acquired (Step S2). Next, it is determined whether β is available or not (Step S15). If the determination in Step S15 is NO, then a request for measurement of blood pressure for calibration is displayed (Step S16). It is determined whether measurement of the blood pressure for calibration has been conducted or not (Step S17). If the determination in Step S17 is YES, the measured PP value, and the acquired PWTT and HR are stored in the register as PP1, PWTT1, and HR1, respectively (Step S18). β is calculated from the Expression 20 (Step S19). If the determination in Step S15 is YES, it is determined whether re-calibration for a should be carried out or not (Step S27). If the determination in Step S27 is YES, then a request for measurement of blood pressure for calibration is displayed (Step S28). It is determined whether measurement of the blood pressure for calibration has been conducted or not (Step S29). If the determination in Step S29 is YES, the measured PP value, and the acquired PWTT and HR are stored in the register as PP2, PWTT2, and HR2, respectively (Step S30). α and β are calculated from following Expressions 22 and 23.PP1=α·PWTT1+β  (Exp. 22)PP2=α·PWTT2+β  (Exp. 23)
If the determination in Step S27 is NO and the processes of Steps S19 and S31, it is determined whether K is available or not (Step S20). If the determination in Step S20 is NO, a request for input of CO value for calibration is displayed (Step S21). It is determined whether the CO value for calibration has been input or not (Step S22). If the determination in Step S22 is YES, the input CO value is stored in the register as CO1 (Step S23). K is calculated from the Expression 21 (Step S24). If the determination in Step S20 is YES, or after K is calculated in Step S24, esCO is calculated from the Expression 15 (Step S25). The esCO acquired in the calculation is displayed (Step S26).
The above procedure is repeated as required.
Alternatively, the measurement of blood pressure for calibration may not be performed, and a blood pressure value which is measured by another sphygmomanometer may be key-input. Furthermore, the peripheral pulse wave may include also that indicative of a volumetric change in addition to the SpO2 pulse wave.
According to JP-A-2005-312947, a method and apparatus for measuring a blood volume, and a biological signal monitoring apparatus can be realized in which variation in hemodynamics of the patient can be monitored always and continuously in an noninvasive manner, a skilled technique of a medical person such as insertion of a catheter is not required, less pain is experienced by the patient, there is no threat of infection because it is noninvasive, and the cost is low.
Also in the above-described method and apparatus for measuring a blood volume, and biological signal monitoring apparatus which are disclosed in JP-A-2005-312947, although improvements are made as compared with the conventional art, calibration in which the CO value for calibration is input substantially at least one time is necessary. In view of the requirement of a skilled technique of a medical person, and the high degree of invasion of the patient, therefore, the monitoring cannot be performed in an easy and continuous manner. Therefore, there is a problem in that the method is difficult to monitor always and continuously variation in hemodynamics of the patient.
In order to solve the problem, there is a related-art method and apparatus for measuring a blood volume, and biological signal monitoring apparatus in which calibration requiring input of CO for calibration is not necessary.
As an example of the related art, an improved example of the procedure shown in FIG. 14 of the conventional art, and in which α is the default value, β and K are acquired by calibration, and then esCO is calculated will be described together with FIG. 2.
Then, the procedure in which a is the default value, β and K are acquired by calibration, and then esCO is calculated will be described with reference to FIG. 2. The calibration of β is carried out when the pulse pressure is not augmented by administration of a vasoconstrictor or the like.
Reading of specific information (sex, age, body height, and body weight) of a patient is carried out (Step S71). Reading of the default value of α is carried out (Step S72). PWTT and HR are acquired (Step S73). Next, it is determined whether β is available or not (Step S74). If the determination in Step S74 is NO, then a request for measurement of blood pressure for calibration is displayed (Step S75). It is determined whether measurement of the blood pressure for calibration has been conducted or not (Step S76). If the determination in Step S76 is YES, the measured value of the blood pressure PP, and acquired PWTT and HR are stored in the register as PP1, PWTT1, and HR1, respectively (Step S77). β is calculated from the Expression 20 (Step S78). If the determination in Step S74 is YES, or after β is calculated in Step S78, it is determined whether K is available or not (Step S79). If the determination in Step S79 is NO, CO1 is calculated by using following Expression 24 (Step S80).CO1=a+b·Sex+c·Age+d·BSA+e·PWTT1+f·HR1·PP1  (Exp. 24)
where BSA (Body Surface Area)=0.007184·(Body Height)0.725·(Body Weight)0.425, and Sex:Male=1, Female=−1.
K is calculated from the Expression 21 (Step S81). If the determination in Step S79 is YES, or after the process of Step S81 is performed, esCO is calculated from the Expression 15 (Step S82). The esCO acquired in the calculation is displayed (Step S83).
The above procedure is repeated as required.
In an apparatus for measuring a blood volume which estimates a blood volume by using a parameter relating to the cardiac output of a subject to be measured, such as the above-described related-art apparatus for measuring a blood volume in which calibration requiring input of CO for calibration is not necessary, and the above-described conventional apparatus for measuring a blood volume disclosed in JP-A-2005-312947 in which calibration requiring input of CO for calibration is necessary, due to an artifact of a biological signal or change of a correlation between a monitoring parameter and a biological signal, accuracy of calculation of an estimated value of the monitoring parameter is lowered, and reliability of a result of measurement of the blood volume is lowered.